PROJECT SUMMARY Eosinophilic esophagitis (EoE) is an increasingly recognized rare disease of children and adults characterized by symptoms including nausea, vomiting, abdominal pain, dysphagia and food impaction that occur in conjunction with esophageal eosinophilia. To date, the only method to make EoE diagnoses and follow treatment responses in EoE is invasive endoscopy with biopsy. While endoscopy is generally safe, an accurate, less invasive, inexpensive, comprehensive and durable test is urgently needed to determine therapeutic efficacy. To address this need, we will use a novel application of an existing technology, the Enterotest (a string-based test used to detect intestinal Giardiasis), to measure esophageal inflammation (herein termed the Esophageal String Test - EST). Our recent publication provides proof-of-principle for the ability of ESTs to capture esophageal inflammatory mediators (biomarkers) in luminal samples from patients affected with EoE, and that these biomarkers correlate with those found in tissue. Our novel Preliminary Data support the rationale and feasibility of sampling EoE-associated inflammatory protein biomarkers in a 1-hour collection time point. These findings provide strong support for using ESTs as novel minimally invasive instruments to monitor therapeutic efficacy in EoE. The global objective of this project is therefore to bring the Esophageal String Test (EST) to commercialization, so that it can be used to monitor therapeutic efficacy in children and adults with EoE. We hypothesize that ESTs will capture an EoE Biomarker Panel (EBP) reflective of disease activity. The Specific Aims are to: (1) Identify an EoE Biomarker Panel (EBP) that will improve the sensitivity and specificity of the EST for monitoring disease activity, and (2) Validate the ability of the EST EBP to monitor therapeutic efficacy in a 1-hour sampling time. Our supportive published and Preliminary Data demonstrate the feasibility of using ESTs in both children and adults with EoE to measure disease activity (esophageal inflammation) in an overnight (12-hour) test, and shorter time periods, currently performed before a scheduled endoscopy with biopsy. In this project, we propose to shorten this time frame to a 1-hour test, a clinically relevant time point that will markedly facilitate its use and potential impact in the outpatient clinic setting. Public Health Relevance/Impacts: At least four major impacts should result from these studies: (1) Identification of an EBP will permit monitoring of esophageal inflammation in EoE; (2) the EBP will be relevant to following disease progression, treatment responses, management and pathogenesis of EoE, (3) validation of the EST EBP will enable development of rapid and inexpensive assays to follow treatment responses, thus reducing the number of follow-up endoscopies with biopsy that are currently performed, and (4) provide a device to monitor EoE disease activity where endoscopy with biopsy may not be available or affordable.